Studies are conducted to define the mechanisms involved in tumor growth and metastasis and to develop new animal models of human cancers. We have found that a basement membrane extract (Matrigel) when premixed with human tumor cells (which do not grow well in mice) promotes their incidence and growth. Very low cell numbers can be used. We have been able to culture new highly differentiated human tumor cells lines from the tumors grown in mice. Laminin, a major basement membrane component, has been found to promote the malignant phenotype. Various biologically active laminin-derived synthetic peptides have been identified. YIGSR from the B1 chain blocks lung colonization, reduces tumor growth, and inhibits angiogenesis. It inhibits tumor growth in the subcutaneous Matrigel model when daily injections are begun 10 days after tumor cell inoculation when the tumors are palpable. Another laminin-derived peptide containing SIKVAV from the A chain has been found to increase tumor growth, lung colonization, and angiogenesis as well as collagenase IV activity and plasminogen activation. Adhesion of cells to these peptides has been used to select for melanoma sub-populations of different malignant potential. The YIGSR adherent cells form more tumors in lung colony assays and larger tumors in the subcutaneous model than the parent cells. The YIGSR non-adherent cells formed the least number of tumors. Our data demonstrate the roles of laminin receptors on tumor cells and of angiogenic factors in regulating tumor growth and spread. Using this information and the newly developed models of human tumors, the development of new therapeutic strategies for cancer should be facilitated.